Kris Wood

Positions:

Associate Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Core Faculty in Innovation & Entrepreneurship

Duke Innovation & Entrepreneurship
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 2002

University of Kentucky, Lexington

Ph.D. 2007

Massachusetts Institute of Technology

Grants:

Medical Scientist Training Program

Administered By
School of Medicine
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Targeting the Hippo pathway in Ras-driven rhabdomyosarcoma

Administered By
Pediatrics, Hematology-Oncology
Awarded By
V Foundation for Cancer Research
Role
Collaborator
Start Date
End Date

Identification and validation of the PAX3-FOXO1 protein interactome

Administered By
Pediatrics, Hematology-Oncology
Awarded By
St. Baldrick's Foundation
Role
Collaborator
Start Date
End Date

RalA signal transduction

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

A Platform for Real-time Drug Profiling of Patient-Derived Melanomas

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Co-Sponsor
Start Date
End Date

Publications:

Vertical Inhibition of the RAF-MEK-ERK Cascade Induces Myogenic Differentiation, Apoptosis and Tumor Regression in H/NRAS Q61X-mutant Rhabdomyosarcoma.

Oncogenic RAS signaling is an attractive target for fusion-negative rhabdomyosarcoma (FN-RMS). Our study validates the role of the ERK MAPK effector pathway in mediating RAS dependency in a panel of H/NRASQ61X-mutant RMS cells and correlates in vivo efficacy of the MEK inhibitor trametinib with pharmacodynamics of ERK activity. A screen is used to identify trametinib-sensitizing targets and combinations are evaluated in cells and tumor xenografts. We find that the ERK MAPK pathway is central to H/NRASQ61X-dependency in RMS cells, however there is poor in vivo response to clinically relevant exposures with trametinib, which correlates with inefficient suppression of ERK activity. CRISPR screening points to vertical inhibition of the RAF-MEK-ERK cascade by co-suppression of MEK and either CRAF or ERK. CRAF is central to rebound pathway activation following MEK or ERK inhibition. Concurrent CRAF suppression and MEK or ERK inhibition, or concurrent pan-RAF and MEK/ERK inhibition (pan-RAFi + MEKi/ERKi), or concurrent MEK and ERK inhibition (MEKi + ERKi) all synergistically block ERK activity and induce myogenic differentiation and apoptosis. In vivo assessment of pan-RAFi + ERKi or MEKi + ERKi potently suppress growth of H/NRASQ61X RMS tumor xenografts, with pan-RAFi + ERKi being more effective and better tolerated. We conclude that CRAF reactivation limits the activity of single agent MEK/ERK inhibitors in FN-RMS. Vertical targeting of the RAF-MEK-ERK cascade, and particularly co-targeting of CRAF and MEK or ERK, or the combination of pan-RAF inhibitors with MEK or ERK inhibitors, have synergistic activity and potently suppress H/NRASQ61X-mutant RMS tumor growth.
Authors
Garcia, N; Del Pozo, V; Yohe, ME; Goodwin, CM; Shackleford, TJ; Wang, L; Baxi, K; Chen, Y; Rogojina, AT; Zimmerman, SM; Peer, CJ; Figg, WD; Ignatius, MS; Wood, KC; Houghton, PJ; Vaseva, AV
MLA Citation
URI
https://scholars.duke.edu/individual/pub1496717
PMID
34737198
Source
pubmed
Published In
Mol Cancer Ther
Published Date
DOI
10.1158/1535-7163.MCT-21-0194

Author Correction: Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.

Authors
Joh, DY; Heggestad, JT; Zhang, S; Anderson, GR; Bhattacharyya, J; Wardell, SE; Wall, SA; Cheng, AB; Albarghouthi, F; Liu, J; Oshima, S; Hucknall, AM; Hyslop, T; Hall, AHS; Wood, KC; Shelley Hwang, E; Strickland, KC; Wei, Q; Chilkoti, A
MLA Citation
Joh, Daniel Y., et al. “Author Correction: Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.Npj Breast Cancer, vol. 7, no. 1, Sept. 2021, p. 126. Pubmed, doi:10.1038/s41523-021-00335-4.
URI
https://scholars.duke.edu/individual/pub1497086
PMID
34535683
Source
pubmed
Published In
Npj Breast Cancer
Volume
7
Published Date
Start Page
126
DOI
10.1038/s41523-021-00335-4

Massively parallel quantification of phenotypic heterogeneity in single-cell drug responses.

[Figure: see text].
Authors
Yellen, BB; Zawistowski, JS; Czech, EA; Sanford, CI; SoRelle, ED; Luftig, MA; Forbes, ZG; Wood, KC; Hammerbacher, J
MLA Citation
Yellen, Benjamin B., et al. “Massively parallel quantification of phenotypic heterogeneity in single-cell drug responses.Sci Adv, vol. 7, no. 38, Sept. 2021, p. eabf9840. Pubmed, doi:10.1126/sciadv.abf9840.
URI
https://scholars.duke.edu/individual/pub1497485
PMID
34533995
Source
pubmed
Published In
Science Advances
Volume
7
Published Date
Start Page
eabf9840
DOI
10.1126/sciadv.abf9840

Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.

Management of breast cancer in limited-resource settings is hindered by a lack of low-cost, logistically sustainable approaches toward molecular and cellular diagnostic pathology services that are needed to guide therapy. To address these limitations, we have developed a multimodal cellphone-based platform-the EpiView-D4-that can evaluate both cellular morphology and molecular expression of clinically relevant biomarkers directly from fine-needle aspiration (FNA) of breast tissue specimens within 1 h. The EpiView-D4 is comprised of two components: (1) an immunodiagnostic chip built upon a "non-fouling" polymer brush-coating (the "D4") which quantifies expression of protein biomarkers directly from crude cell lysates, and (2) a custom cellphone-based optical microscope ("EpiView") designed for imaging cytology preparations and D4 assay readout. As a proof-of-concept, we used the EpiView-D4 for assessment of human epidermal growth factor receptor-2 (HER2) expression and validated the performance using cancer cell lines, animal models, and human tissue specimens. We found that FNA cytology specimens (prepared in less than 5 min with rapid staining kits) imaged by the EpiView-D4 were adequate for assessment of lesional cellularity and tumor content. We also found our device could reliably distinguish between HER2 expression levels across multiple different cell lines and animal xenografts. In a pilot study with human tissue (n = 19), we were able to accurately categorize HER2-negative and HER2-positve tumors from FNA specimens. Taken together, the EpiView-D4 offers a promising alternative to invasive-and often unavailable-pathology services and may enable the democratization of effective breast cancer management in limited-resource settings.
Authors
Joh, DY; Heggestad, JT; Zhang, S; Anderson, GR; Bhattacharyya, J; Wardell, SE; Wall, SA; Cheng, AB; Albarghouthi, F; Liu, J; Oshima, S; Hucknall, AM; Hyslop, T; Hall, AHS; Wood, KC; Shelley Hwang, E; Strickland, KC; Wei, Q; Chilkoti, A
MLA Citation
Joh, Daniel Y., et al. “Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.Npj Breast Cancer, vol. 7, no. 1, July 2021, p. 85. Pubmed, doi:10.1038/s41523-021-00290-0.
URI
https://scholars.duke.edu/individual/pub1487266
PMID
34215753
Source
pubmed
Published In
Npj Breast Cancer
Volume
7
Published Date
Start Page
85
DOI
10.1038/s41523-021-00290-0

Abstract 6406: FAK and MEK co-targeting: A new multimodal precision therapy forGNAQ-driven uveal melanoma

Authors
Paradis, JS; Acosta, M; Arang, N; Saddawi-Konefka, R; Kishore, A; Sugase, T; Feng, X; Wood, KC; Coma, S; Terai, M; Sato, T; Pachter, JA; Gutkind, JS
MLA Citation
Paradis, Justine S., et al. “Abstract 6406: FAK and MEK co-targeting: A new multimodal precision therapy forGNAQ-driven uveal melanoma.” Experimental and Molecular Therapeutics, American Association for Cancer Research, 2020. Crossref, doi:10.1158/1538-7445.am2020-6406.
URI
https://scholars.duke.edu/individual/pub1475572
Source
crossref
Published In
Experimental and Molecular Therapeutics
Published Date
DOI
10.1158/1538-7445.am2020-6406